N-METHYL-N'-NITRO-N-NITROSOGUANIDINE (MNNG) (Group 2A)

Three cases of brain tumour (gliomas) and one of colon cancer have been reported
from a genetics laboratory over a 13-year period. All the subjects
were likely to have been exposed to MNNG for at least six to 15 years
prior to death, but other carcinogens had been used in the laboratory
[ref: 1,2].

B. Evidence for carcinogenicity to animals (sufficient)

MNNG has been tested for carcinogenicity in mice, rats, hamsters,
rabbits and dogs, producing tumours at many sites. It has a
predominantly local carcinogenic effect and is carcinogenic in
single-dose experiments. Following its oral administration,
papillomas and squamous-cell carcinomas of the oesophagus and
forestomach, adenocarcinomas of the stomach, small intestine and large
bowel, and sarcomas of the gastrointestinal tract were reported [ref:
3]. These findings have been extended in more recent studies after
oral administration to rats [ref: 4-7], hamsters [ref: 8,9] and dogs
[ref: 10,11]. After subcutaneous injection in mice, it produced lung
and liver tumours and haemangioendotheliomas [ref: 12]; after
intrarectal instillation in rats and guinea-pigs [ref: 13-15] and
after intrauterine and intravaginal application to rats, it produced
local tumours [ref: 16].

C. Other relevant data

MNNG is an alkylating agent [ref: 17]. No data were available to
evaluate the genetic and related effects of this compound in humans.

MNNG induced DNA strand breaks in various organs of rats treated
in vivo. It did not cause dominant lethal mutations in mice, but it
gave positive results for mutation in the mouse spot test; it induced
chromosomal aberrations and micronuclei in bone-marrow cells of mice and sister chromatid exchanges in bone-marrow cells of mice and
Chinese hamsters treated in vivo. It induced chromosomal aberrations,
sister chromatid exchanges, DNA strand breaks and unscheduled DNA
synthesis in human and rodent cells in vitro and induced mutation
in cultured rodent cells. It gave positive results in several assays
for cell transformation. MNNG induced somatic and sex-linked recessive
lethal mutations in Drosophila. It caused chromosomal aberrations,
sister chromatid exchanges and mutation in plants and recombination
and mutation in fungi. It was mutagenic to and caused DNA damage in
bacteria, and gave positive results in host-mediated assays using
bacteria or yeast as indicators and mice as hosts [ref: 17].